The broad objectives of the proposed research are to study the mechanisms involved in aerosol allergen-induced asthma, the clinical relevance and mechanisms of airway responsiveness to inhaled histamine, methacholine and prostaglandin F2 alpha, (especially in relation to asthma severity) and to correlate measured changes in various pulmonary functions to urinary excretion rate and plasma concentrations of histamine, norepinephrine, epinephrine, cyclic AMP and cyclic GMP. Studies of these metabolites will also be conducted in patients with exercise-induced asthma and cold air-induced asthma. The effect of corticosteroids, cromolyn derivatives and other drugs on early and late asthmatic responses and on changes in the metabolites will be investigated. Pulmonary functions will be measured by standard spirometric and plethysmographic techniques following inhalation of allergen, histamine, methacholine or PGE2 alpha by a carefully standardized inhalation technique. Catecholamines are measured by a fluorescence technique, the cyclic nucleotides by radioimmunoassay and histamine by an enzymatic isotopic technique. These studies should provide useful information on the mechanisms of airway hyper-responsiveness in asthma, and integrated assessment of the changes in histamine, norepinephrine, epinephrine, cyclic AMP and cyclic GMP in controlled induced asthma and the effect of various drugs on these parameters. A comparison of the effects of histamine, methacholine and PGF 2 alpha in normal and asthmatic subjects will also provide new data on the possibility of reduced sympathoadrenal activation in asthma.